Research is directed toward genetic mechanisms controlling cellular differentiation in the eukaryote, Drosophila. It assumes that cytodifferentiation involves, in part, differential gene activity and control of the synthesis of given proteins at specific times and places in the various cells and tissues of the developing organism. The approach being used to elucidate controlling mechanisms in the selection of a specific protein as an indicator of the state of differentiation of a tissue, and the analysis of factors that regulate its synthesis, properties, location and ultimate fate. gamma-Amylases of Drosophila were chosen as particularly well-suited for this type of analysis because of the: 1) enzyme's properties, e.g. stability, 2) unique features of the cells that secrete it, e.g. polytene chromosomes, and 3) cumulative knowledge of the genetics of the organism producing it. A system is being developed to selectively screen for mutations of "regulatory genes" that control the structural gene for amylase. This gene, Amy, has been located genetically and cytogenetically by means of electrophoretic variants of the enzyme in D. melanogaster and D. hydei. Amy is tandemly duplicated in the former species; yet, the duplicated loci, or their products, are independently regulated. In D. hydei, where Amy is not duplicated, "puffing" at what appears to be the Amy locus in midgut cells can be induced by dietary means, correlating with enhanced amylase activity. Thus, mutants altering this cytological sign of transcription may be selected. Amylases from both species have been purified and are being characterized. In D. hydei, labelled antibodies to amylase will be used to study its intracellular distribution and to quantitate de novo synthesis. Mutants controlling amylase at the translational level, or higher, may thus be distinguished and analyzed. Exposure of such regulatory factors and their mechanism of action would have far-reaching implications for developmental genetics and biology as a whole.